Monoclonal Antibodies Against Toxic Shock Syndrome Toxin-1 And Their Use In Diagnosis

Toxic shock syndrome toxin -1 (TSST-1) is a 22kDa extracellular protein produced by some strains of Staphylococcus aureus. It is implicated in the pathogenesis of toxic shock syndrome, an acute life-threatening multisystem disease. Eight hybridoma cell lines producing monoclonal antibodies with high binding affinity to TSST-1 have been produced and a monoclonal antibody based enzyme-linked immunosorbant assay developed. This assay is specific for TSST-1 and no cross reaction with a number of other bacterial toxins has been observed. The ELISA has been amplified enzymically using biotinylated tyramine and streptavidin peroxidase to detect as little as 0.1ng ml-1 of toxin. Competitive binding studies have indicated the presence of at least three antigenic sites on the toxin. The ability of these antibodies to inhibit the mitogenic activity of the toxin in T-cell proliferation assays using mouse and human lymphocytes has been assessed and results of this work indicate that one of the major antigenic sites has an important role in the mitogenicity of the toxin. Binding of the antibodies has been localised to the carboxyl terminal region which has been implicated in the biological activity of the toxin and several antigenic determinants were identified in this region by epitope mapping using polyclonal antibody

Ordovician, Silurian, and middle Devonian stratigraphy in northwestern Kentucky and southern Indiana: some reinterpretations

Field trip 8 for the Annual Meeting of the Geological Society of America, Cincinnati, Ohio, October 26-29, 1992

CCN5/WISP2 and metabolic diseases.

This is the final version of the article. It first appeared from Springer via https://doi.org/10.1007/s12079-017-0437-zObesity and type 2 diabetes increase worldwide at an epidemic rate. It is expected that by the year 2030 around 500 million people will have diabetes; predominantly type 2 diabetes. The CCN family of proteins has become of interest in both metabolic and other common human diseases because of their effects on mesenchymal stem cell (MSCs) proliferation and differentiation as well as being important regulators of fibrosis. We here review current knowledge of the WNT1 inducible signaling pathway protein 2 (CCN5/WISP2). It has been shown to be an important regulator of both these processes through effects on both the canonical WNT and the TGFβ pathways. It is also under normal regulation by the adipogenic commitment factor BMP4, in contrast to conventional canonical WNT ligands, and allows MSCs to undergo normal adipose cell differentiation. CCN5/WISP2 is highly expressed in, and secreted by, MSCs and is an important regulator of MSCs growth. In a transgenic mouse model overexpressing CCN5/WISP2 in the adipose tissue, we have shown that it is secreted and circulating in the blood, the mice develop hypercellular white and brown adipose tissue, have increased lean body mass and enlarged hypercellular hearts. Obese transgenic mice had improved insulin sensitivity. Interestingly, the anti-fibrotic effect of CCN5/WISP2 is protective against heart failure by inhibition of the TGFβ pathway. Understanding how CCN5/WISP2 is regulated and signals is important and may be useful for developing new treatment strategies in obesity and metabolic diseases and it can also be a target in regenerative medicine.The studies in the authors’ laboratory are supported by grants from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement (n° 608765), Henning and Johan Throne- Holst’s foundation for the promotion of scientific research, the Medical Research Council, Torsten Söderberg Foundation, Novo Nordisk Foundation, EFSD, Swedish Diabetes Foundation, Swedish ALF funds, Edgar Sjölund Foundation, Wilhelm and Martina Lundgren’s Foundation, the Magnus Bergvall Foundation, Lisa and Johan Grönberg Foundation, Göteborgs Diabetesförening, Sigurd and Elsa Golje’s Foundation, and the EU’s FP7 program (n°607842)

Reinforced composite flywheels and shafts

The maximum safe operating speed or flywheels and shafts made of low tensile strength material is often determined by the speed at which radial tensile stress exceeds a radial tensile stress limit for the material. Circumferentially wound fiber composite material, for example, has a relatively low tensile strength along the radial direction perpendicular to the fibers. To increase the maximum safe operating speed, it is therefore desirable to form a fiber composite flywheel or shaft with radial compressive prestress. Such a prestressed flywheel or shaft has an outer annulus and an inner cylinder disposed in the outer annulus, and an annular layer of solidified bonding agent within an annular region between the outer annulus and the inner cylinder, wherein the outer annulus and the inner cylinder include substantial radial prestress induced by the bonding agent. The rim portion of a flywheel, for example, is formed from an outer ring (the annulus) and an inner ring (the cylinder, which is hollow in this case). Large, thick flywheels preferably have multiple cylindrical sections joined by such layers of bonding agent, and a plurality of the cylindrical sections each including an outer layer of relatively stiff fiber-composite material, and an inner layer of relatively compliant fiber-composite material within an integral matrix material.Board of Regents, University of Texas Syste

Rhoptry proteins ROP5 and ROP18 are major murine virulence factors in genetically divergent South American strains of Toxoplasma gondii

Toxoplasma gondii has evolved a number of strategies to evade immune responses in its many hosts. Previous genetic mapping of crosses between clonal type 1, 2, and 3 strains of T. gondii, which are prevalent in Europe and North America, identified two rhoptry proteins, ROP5 and ROP18, that function together to block innate immune mechanisms activated by interferon gamma (IFNg) in murine hosts. However, the contribution of these and other virulence factors in more genetically divergent South American strains is unknown. Here we utilized a cross between the intermediately virulent North American type 2 ME49 strain and the highly virulent South American type 10 VAND strain to map the genetic basis for differences in virulence in the mouse. Quantitative trait locus (QTL) analysis of this new cross identified one peak that spanned the ROP5 locus on chromosome XII. CRISPR-Cas9 mediated deletion of all copies of ROP5 in the VAND strain rendered it avirulent and complementation confirmed that ROP5 is the major virulence factor accounting for differences between type 2 and type 10 strains. To extend these observations to other virulent South American strains representing distinct genetic populations, we knocked out ROP5 in type 8 TgCtBr5 and type 4 TgCtBr18 strains, resulting in complete loss of virulence in both backgrounds. Consistent with this, polymorphisms that show strong signatures of positive selection in ROP5 were shown to correspond to regions known to interface with host immunity factors. Because ROP5 and ROP18 function together to resist innate immune mechanisms, and a significant interaction between them was identified in a two-locus scan, we also assessed the role of ROP18 in the virulence of South American strains. Deletion of ROP18 in South American type 4, 8, and 10 strains resulted in complete attenuation in contrast to a partial loss of virulence seen for ROP18 knockouts in previously described type 1 parasites. These data show that ROP5 and ROP18 are conserved virulence factors in genetically diverse strains from North and South America, suggesting they evolved to resist innate immune defenses in ancestral T. gondii strains, and they have subsequently diversified under positive selection

How Public Private Partnerships Support Climate Mitigation and Adaptation Agenda in Cities

Climate change has become a major issue in cities that champion the path to the sustainable development of cities. Recent effort by COP 26 has buoyed the emphasis for improving neighborliness of climate and humankind. Since cities anchor national prosperity and act as and centre for policy making and actions for the country, they act as an important administrative structure for championing climate agenda. Although the literature on adaptation to climate change is rapidly expanding, little is known about how the adoption of new public management tool, public private partnerships(PPPs) contribute to climate sustainability, yet the adoption of PPPs is on the rise in traditional and emerging smart cities. Based on a review of literature, this study provides insights on how PPPs can enable city administrations to play a key role for supporting climate sustainable agenda of nations especially in Sub Saharan Africa that is considered a victim of climate change and yet this part of the world is deemed to have been insignificantly responsible for the climate change by largely affected negative effects of today’s climate change

EVALUATING THE EFFECTS OF MONENSIN OVERDOSE IN DAIRY CATTLE

Monensin is approved as a feed additive by the FDA Center for Veterinary Medicine to increase milk production efficiency in lactating dairy cattle. To assess the effects of a gross error in mixing monensin into cattle feed, a 10-fold overdose was given for three consecutive days to naïve cows as well as cows previously dosed with monensin within the label range. Cows were evaluated during the overdose and for a subsequent 4 week observation period. Physiological variables were analyzed, including dry matter intake, body weight, body condition score, and serum chemistry profile. Production variables were analyzed, including milk yield and milk composition. Cows were blocked according to pre-treatment milk output, days in milk, and body condition. Results were analyzed using linear mixed model methodology with a baseline covariate. The study provided information for the veterinarian and the dairy farmer for determining whether an overdose may have occurred, for assessing the prognosis, and for deciding whether to continue feeding monensin immediately following an overdose